BRAF^(V600E)基因突变检测在细针穿刺细胞学良性甲状腺结节中的应用价值  

The application value of BRAF^(V600E)gene mutation testing in fineneedle aspiration biopsy diagnosed benign thyroid nodules

作　　者：蔡文卿 崔灿 刘洁 陈卓[1] 韩欣冉 吴可 刘美琪 吴境 刘晓莉[1] CAI Wenqing;CUI Can;LIU Jie;CHEN Zhuo;HAN Xinran;WU Ke;LIU Meiqi;WU Jing;LIU Xiaoli(Department of Thyroid Surgery,China-Japan Union Hospital of Jilin University,Changchun 130033,China;Second Department of General Surgery,Dandong First Hospital,Dandong,Liaoning 118001,China)

机构地区：[1]吉林大学中日联谊医院甲状腺外科,吉林长春130033 [2]辽宁省丹东市第一医院普外二科,辽宁丹东118001

出　　处：《中国普通外科杂志》2024年第11期1786-1793,共8页China Journal of General Surgery

基　　金：吉林省卫生科研人才专项基金资助项目(2023SCZ37);吉林省自然科学基金资助项目(YDZJ202401159ZYTS)。

摘　　要：背景与目的:细针穿刺细胞学(FNA)因所获取样本量较少等原因,其局限性包括标本无法诊断、细胞学结果不确定、假阴性及假阳性结果等,易造成患者漏诊或误诊。鼠类肉瘤滤过性毒菌致癌同源体B1(BRAF)突变作为甲状腺乳头状癌(PTC)的特异性生物标志,在FNA良性高风险结节中诊断价值目前研究较少。因此,本研究进一步探讨FNA良性甲状腺结节中附加BRAF^(V600E)基因突变检测的临床价值。方法:回顾性分析2019年1月—2022年9月吉林大学中日联谊医院甲状腺外科549例经668次超声提示PTC高风险、TIRADS分级为4~5类结节患者的临床资料。所有患者均接受手术治疗并于术后对切除组织进行石蜡病理学检查,根据纳入和排除标准,共84枚FNA良性结节纳入本研究,分析BRAF^(V600E)基因突变患者的临床病理特征;以术后病理结果为金标准,分析BRAF^(V600E)基因突变检测对FNA良性结节中的诊断效能。结果:84枚FNA良性甲状腺结节中,44枚(52.4%)BRAF^(V600E)基因突变检测阳性。BRAF^(V600E)基因突变阳性患者中年龄<45岁的患者占比明显高于BRAF^(V600E)基因突变阴性组患者(56.8%vs.35.0%,P=0.045)、结节中位长径明显小于BRAF^(V600E)基因突变阴性组(0.49 cm vs.0.61 cm,P=0.024)。术后病理提示,63枚甲状腺结节为PTC结节,21枚为良性结节;PTC组结节的中位长径小于良性结节(0.50 cm vs.0.70 cm,P=0.004)、结节<1 cm的占比高于良性结节组(95.2%vs.71.4%,P=0.007)、BRAF^(V600E)基因突变检出率高于良性组(68.3%vs.4.8%,P<0.001)。在甲状腺结节超声特征中,BRAF^(V600E)基因突变阳性组甲状腺结节边缘模糊/不规则发生率明显高于阴性组(86.4%vs.60.0%,P=0.006);PTC结节边缘模糊/不规则发生率高于良性结节(81.0%vs.52.4%,P=0.010)。多因素Logistic回归分析结果显示,BRAF^(V600E)基因突变阳性的甲状腺结节诊断为PTC的风险是BRAF^(V600E)基因突变阴性结节的39.184倍(P=0.001),BRAF^(V600E)�Background and Aims:Fine-needle aspiration cytology(FNA)has limitations due to the small sample size obtained,including nondiagnostic specimens,indeterminate cytological results,and false-negative or false-positive results,potentially leading to misdiagnosis or missed diagnoses.The BRAF gene mutation,specifically BRAF^(V600E),is a specific biomarker for papillary thyroid carcinoma(PTC).However,studies on its diagnostic value in FNA benign high-risk thyroid nodules are limited.This study was conducted to further explore the clinical value of adding BRAF^(V600E)mutation testing in FNA benign thyroid nodules.Methods:A retrospective analysis was conducted on the clinical data of 549 patients who underwent 668 ultrasound evaluations indicating high risk of PTC and were classified as TIRADS categories 4-5 thyroid nodules at the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University from January 2019 to September 2022.All patients underwent surgical treatment,and paraffin pathological examination was performed on resected tissues after surgery.Based on inclusion and exclusion criteria,84 FNA benign thyroid nodules were included in this study.The clinicopathologic characteristics of nodules with BRAF^(V600E)mutations were analyzed.Using postoperative pathology as the gold standard,the diagnostic performance of BRAF^(V600E)mutation testing in FNA benign nodules was assessed.Results:Among the 84 FNA benign thyroid nodules,44(52.4%)tested positive for the BRAF^(V600E)mutation.Patients with BRAF^(V600E)-positive nodules were more likely to be younger than 45 years(56.8%vs.35.0%,P=0.045),and their nodules had a smaller median long diameter compared to the BRAF^(V600E)negative group(0.49 cm vs.0.61 cm,P=0.024).Postoperative pathology revealed 63 PTC nodules and 21 benign nodules.PTC nodules had a smaller median long diameter than benign nodules(0.50 cm vs.0.70 cm,P=0.004)and a higher proportion of nodules<1 cm(95.2%vs.71.4%,P=0.007),with a higher BRAF^(V600E)mutation rate(68.3%vs.4.8%,P<0.001).In terms of

关 键 词：甲状腺肿瘤 甲状腺癌 乳头状 细针抽吸活检 原癌基因蛋白质B-raf 

分 类 号：R736.1[医药卫生—肿瘤]